Selective Regulation of Arterial Branching Morphogenesis by Synectin

Thomas W. Chittenden, Filip Claes, Anthony A. Lanahan, Monica Autiero, Robert T. Palac, Eugene V. Tkachenko, Arye Elfenbein, Carmen Ruiz de Almodovar, Eduard Dedkov, Robert Tomanek, Weiming Li, Michael Westmore, Jai Pal Singh, Arie Horowitz, Mary Jo Mulligan-Kehoe, Karen L. Moodie, Zhen W. Zhuang, Peter Carmeliet, Michael Simons

Research output: Contribution to journalArticle

111 Scopus citations

Abstract

Branching morphogenesis is a key process in the formation of vascular networks. To date, little is known regarding the molecular events regulating this process. We investigated the involvement of synectin in this process. In zebrafish embryos, synectin knockdown resulted in a hypoplastic dorsal aorta and hypobranched, stunted, and thin intersomitic vessels due to impaired migration and proliferation of angioblasts and arterial endothelial cells while not affecting venous development. Synectin-/- mice demonstrated decreased body and organ size, reduced numbers of arteries, and an altered pattern of arterial branching in multiple vascular beds while the venous system remained normal. Murine synectin-/- primary arterial, but not venous, endothelial cells showed decreased in vitro tube formation, migration, and proliferation and impaired polarization due to abnormal localization of activated Rac1. We conclude that synectin is involved in selective regulation of arterial, but not venous, growth and branching morphogenesis and that Rac1 plays an important role in this process.

Original languageEnglish (US)
Pages (from-to)783-795
Number of pages13
JournalDevelopmental Cell
Volume10
Issue number6
DOIs
StatePublished - Jun 1 2006

Keywords

  • DEVBIO
  • SIGNALING

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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    Chittenden, T. W., Claes, F., Lanahan, A. A., Autiero, M., Palac, R. T., Tkachenko, E. V., Elfenbein, A., Ruiz de Almodovar, C., Dedkov, E., Tomanek, R., Li, W., Westmore, M., Singh, J. P., Horowitz, A., Mulligan-Kehoe, M. J., Moodie, K. L., Zhuang, Z. W., Carmeliet, P., & Simons, M. (2006). Selective Regulation of Arterial Branching Morphogenesis by Synectin. Developmental Cell, 10(6), 783-795. https://doi.org/10.1016/j.devcel.2006.03.012